Effects of Cooking with Liquefied Petroleum Gas or Biomass on Stunting in Infants.

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are presented in the current report - stunting (defined as a length-for-age z score that was more than two standard deviations below the median of a growth standard) at 12 months of age - was one of four primary outcomes of the trial. Intention-to-treat analyses were performed to estimate the relative risk of stunting. RESULTS: Adherence to the intervention was high, and the intervention resulted in lower prenatal and postnatal 24-hour personal exposures to fine particulate matter than the control (mean prenatal exposure, 35.0 µg per cubic meter vs. 103.3 µg per cubic meter; mean postnatal exposure, 37.9 µg per cubic meter vs. 109.2 µg per cubic meter). Among 3061 live births, 1171 (76.2%) of the 1536 infants born to women in the intervention group and 1186 (77.8%) of the 1525 infants born to women in the control group had a valid length measurement at 12 months of age. Stunting occurred in 321 of the 1171 infants included in the analysis (27.4%) of the infants born to women in the intervention group and in 299 of the 1186 infants included in the analysis (25.2%) of those born to women in the control group (relative risk, 1.10; 98.75% confidence interval, 0.94 to 1.29; P = 0.12). CONCLUSIONS: An intervention strategy starting in pregnancy and aimed at mitigating household air pollution by replacing biomass fuel with LPG for cooking did not reduce the risk of stunting in infants. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Liquefied Petroleum Gas or Biomass Cooking and Severe Infant Pneumonia.

BACKGROUND: Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS: We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS: Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM2.5 among the children, with a median exposure of 24.2 µg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 µg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS: The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Liquefied Petroleum Gas or Biomass for Cooking and Effects on Birth Weight.

BACKGROUND: Exposure during pregnancy to household air pollution caused by the burning of solid biomass fuel is associated with adverse health outcomes, including low birth weight. Whether the replacement of a biomass cookstove with a liquefied petroleum gas (LPG) cookstove would result in an increase in birth weight is unclear. METHODS: We performed a randomized, controlled trial involving pregnant women (18 to <35 years of age and at 9 to <20 weeks' gestation as confirmed on ultrasonography) in Guatemala, India, Peru, and Rwanda. The women were assigned in a 1:1 ratio to use a free LPG cookstove and fuel (intervention group) or to continue using a biomass cookstove (control group). Birth weight, one of four prespecified primary outcomes, was the primary outcome for this report; data for the other three outcomes are not yet available. Birth weight was measured within 24 hours after birth. In addition, 24-hour personal exposures to fine particulate matter (particles with a diameter of ≤2.5 µm [PM2.5]), black carbon, and carbon monoxide were measured at baseline and twice during pregnancy. RESULTS: A total of 3200 women underwent randomization; 1593 were assigned to the intervention group, and 1607 to the control group. Uptake of the intervention was nearly complete, with traditional biomass cookstoves being used at a median rate of less than 1 day per month. After randomization, the median 24-hour personal exposure to fine particulate matter was 23.9 µg per cubic meter in the intervention group and 70.7 µg per cubic meter in the control group. Among 3061 live births, a valid birth weight was available for 94.9% of the infants born to women in the intervention group and for 92.7% of infants born to those in the control group. The mean (±SD) birth weight was 2921±474.3 g in the intervention group and 2898±467.9 g in the control group, for an adjusted mean difference of 19.6 g (95% confidence interval, -10.1 to 49.2). CONCLUSIONS: The birth weight of infants did not differ significantly between those born to women who used LPG cookstoves and those born to women who used biomass cookstoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Heat Exposure among Adult Women in Rural Tamil Nadu, India.

Exposure to heat is associated with a substantial burden of disease and is an emerging issue in the context of climate change. Heat is of particular concern in India, which is one of the world's hottest countries and also most populous, where relatively little is known about personal heat exposure, particularly in rural areas. Here, we leverage data collected as part of a randomized controlled trial to describe personal temperature exposures of adult women (40-79 years of age) in rural Tamil Nadu. We also characterize measurement error in heat exposure assessment by comparing personal exposure measurements to the nearest ambient monitoring stations and to commonly used modeled temperature data products. We find that temperatures differ across individuals in the same area on the same day, sometimes by more than 5 °C within the same hour, and that some individuals experience sharp increases in heat exposure in the early morning or evening, potentially a result of cooking with solid fuels. We find somewhat stronger correlations between the personal exposure measurements and the modeled products than with ambient monitors. We did not find evidence of systematic biases, which indicates that adjusting for discrepancies between different exposure measurement methods is not straightforward.

Factors Determining Black Carbon Exposures among Pregnant Women Enrolled in the HAPIN Trial.

Residential biomass burning is an important source of black carbon (BC) exposure among rural communities in low- and middle-income countries. We collected 7165 personal BC samples and individual/household level information from 3103 pregnant women enrolled in the Household Air Pollution Intervention Network trial. Women in the intervention arm received free liquefied petroleum gas stoves and fuel throughout pregnancy; women in the control arm continued the use of biomass stoves. Median (IQR) postintervention BC exposures were 9.6 µg/m3 (5.2-14.0) for controls and 2.8 µg/m3 (1.6-4.8) for the intervention group. Using mixed models, we characterized predictors of BC exposure and assessed how exposure contrasts differed between arms by select predictors. Primary stove type was the strongest predictor (R2 = 0.42); the models including kerosene use, kitchen location, education, occupation, or stove use hours also provided additional explanatory power from the base model adjusted only for the study site. Our full, trial-wide, model explained 48% of the variation in BC exposures. We found evidence that the BC exposure contrast between arms differed by study site, adherence to the assigned study stove, and whether the participant cooked. Our findings highlight factors that may be addressed before and during studies to implement more impactful cookstove intervention trials.

Resources and Geographic Access to Care for Severe Pediatric Pneumonia in Four Resource-limited Settings.

Rationale: Pneumonia is the leading cause of death in children worldwide. Identifying and appropriately managing severe pneumonia in a timely manner improves outcomes. Little is known about the readiness of healthcare facilities to manage severe pediatric pneumonia in low-resource settings. Objectives: As part of the HAPIN (Household Air Pollution Intervention Network) trial, we sought to identify healthcare facilities that were adequately resourced to manage severe pediatric pneumonia in Jalapa, Guatemala (J-GUA); Puno, Peru (P-PER); Kayonza, Rwanda (K-RWA); and Tamil Nadu, India (T-IND). We conducted a facility-based survey of available infrastructure, staff, equipment, and medical consumables. Facilities were georeferenced, and a road network analysis was performed. Measurements and Main Results: Of the 350 healthcare facilities surveyed, 13% had adequate resources to manage severe pneumonia, 37% had pulse oximeters, and 44% had supplemental oxygen. Mean (±SD) travel time to an adequately resourced facility was 41 ± 19 minutes in J-GUA, 99 ± 64 minutes in P-PER, 40 ± 19 minutes in K-RWA, and 31 ± 19 minutes in T-IND. Expanding pulse oximetry coverage to all facilities reduced travel time by 44% in J-GUA, 29% in P-PER, 29% in K-RWA, and 11% in T-IND (all P < 0.001). Conclusions: Most healthcare facilities in low-resource settings of the HAPIN study area were inadequately resourced to care for severe pediatric pneumonia. Early identification of cases and timely referral is paramount. The provision of pulse oximeters to all health facilities may be an effective approach to identify cases earlier and refer them for care and in a timely manner.

Study design and rationale for a cluster randomized trial of a safe child feces management intervention in rural Odisha, India.

BACKGROUND: Poor child feces management (CFM) is believed to be an important source of exposure to enteric pathogens that contribute to a large disease burden in low-income settings. While access to sanitation facilities is improving, national surveys indicate that even households with latrines often do not safely dispose of their child's feces. Working with caregivers in rural Odisha, India, we co-developed an intervention aimed at improving safe disposal of child feces and encouraging child latrine use at an earlier age. We describe the rationale for the intervention and summarize the protocol for a cluster randomized trial (CRT) to evaluate its effectiveness at changing CFM practices. METHODS: The intervention consists of six behavior change strategies together with hardware provision: wash basin and bucket with lid to aid safe management of soiled nappies and a novel latrine training mat to aid safe disposal and latrine training. The intervention will be offered at the village level to interested caregivers of children < 5 years of age by a community-based organization. Following a baseline survey, 74 villages were randomly allocated to either intervention or control arm. The primary outcome is caregiver reported safe disposal of child feces after last defecation, either by the caregiver disposing of the child's feces into the latrine or the child using the latrine, measured approximately four to six months following intervention delivery. Secondary outcomes include fecal contamination of household drinking water and the childs' hands. A process evaluation will also be conducted to assess intervention fidelity and reach, and explore implementer and participant feedback. DISCUSSION: This study addresses a crucial knowledge gap in sanitation by developing a scalable intervention to improve safe management of child feces. The behavior change strategies were designed following the Risks, Attitudes, Norms, Abilities and Self-Regulation (RANAS) approach, which has shown to be effective for other environmental behavior change interventions in low-income settings. The latrine training mat hardware is a novel design developed cooperatively and manufactured locally. The evaluation follows a rigorous CRT study design assessing the impact of the intervention on CFM behavior change, as well as fecal contamination of two sources of potential exposure. TRIAL REGISTRATION: This trial is registered at ISRCTN: ISRCTN15831099.

Sand Barriers around Latrine Pits Reduce Fecal Bacterial Leaching into Shallow Groundwater: A Randomized Controlled Trial in Coastal Bangladesh.

We evaluated the effectiveness of a sand barrier around latrine pits in reducing fecal indicator bacteria (FIB) leaching into shallow groundwater. We constructed 68 new offset single pit pour flush latrines in the Galachipa subdistrict of coastal Bangladesh. We randomly assigned 34 latrines to include a 50 cm thick sand barrier under and around the pit and 34 received no sand barrier. Four monitoring wells were constructed around each pit to collect water samples at baseline and subsequent nine follow-up visits over 24 months. Samples were tested using the IDEXX Colilert method to enumerate E. coli and thermotolerant coliforms most probable number (MPN). We determined the difference in mean log10MPN FIB counts/100 mL in monitoring well samples between latrines with and without a sand barrier using multilevel linear models and reported cluster robust standard error. The sand barrier latrine monitoring well samples had 0.38 mean log10MPN fewer E. coli (95% CI: 0.16, 0.59; p = 0.001) and 0.38 mean log10MPN fewer thermotolerant coliforms (95% CI: 0.14, 0.62; p = 0.002), compared to latrines without sand barriers, a reduction of 27% E. coli and 24% thermotolerant coliforms mean counts. A sand barrier can modestly reduce the risk presented by pit leaching.

Active trachoma and community use of sanitation, Ethiopia.

OBJECTIVE: To investigate, in Amhara, Ethiopia, the association between prevalence of active trachoma among children aged 1-9 years and community sanitation usage. METHODS: Between 2011 and 2014, prevalence of trachoma and household pit latrine usage were measured in five population-based cross-sectional surveys. Data on observed indicators of latrine use were aggregated into a measure of community sanitation usage calculated as the proportion of households with a latrine in use. All household members were examined for clinical signs, i.e. trachomatous inflammation, follicular and/or intense, indicative of active trachoma. Multilevel logistic regression was used to estimate prevalence odds ratios (OR) and 95% confidence intervals (CI), adjusting for community, household and individual factors, and to evaluate modification by household latrine use and water access. FINDINGS: In surveyed areas, prevalence of active trachoma among children was estimated to be 29% (95% CI: 28-30) and mean community sanitation usage was 47% (95% CI: 45-48). Despite significant modification (p < 0.0001), no pattern in stratified ORs was detected. Summarizing across strata, community sanitation usage values of 60 to < 80% and ≥ 80% were associated with lower prevalence odds of active trachoma, compared with community sanitation usage of < 20% (OR: 0.76; 95% CI: 0.57-1.03 and OR: 0.67; 95% CI: 0.48-0.95, respectively). CONCLUSION: In Amhara, Ethiopia, a negative correlation was observed between community sanitation usage and prevalence of active trachoma among children, highlighting the need for continued efforts to encourage higher levels of sanitation usage and to support sustained use throughout the community, not simply at the household level.

Behavioral Reactivity Associated With Electronic Monitoring of Environmental Health Interventions--A Cluster Randomized Trial with Water Filters and Cookstoves.

Subject reactivity--when research participants change their behavior in response to being observed--has been documented showing the effect of human observers. Electronics sensors are increasingly used to monitor environmental health interventions, but the effect of sensors on behavior has not been assessed. We conducted a cluster randomized controlled trial in Rwanda among 170 households (70 blinded to the presence of the sensor, 100 open) testing whether awareness of an electronic monitor would result in a difference in weekly use of household water filters and improved cookstoves over a four-week surveillance period. A 63% increase in number of uses of the water filter per week between the groups was observed in week 1, an average of 4.4 times in the open group and 2.83 times in the blind group, declining in week 4 to an insignificant 55% difference of 2.82 uses in the open, and 1.93 in the blind. There were no significant differences in the number of stove uses per week between the two groups. For both filters and stoves, use decreased in both groups over four-week installation periods. This study suggests behavioral monitoring should attempt to account for reactivity to awareness of electronic monitors that persists for weeks or more.

Process evaluation and assessment of use of a large scale water filter and cookstove program in Rwanda.

BACKGROUND: In an effort to reduce the disease burden in rural Rwanda, decrease poverty associated with expenditures for fuel, and minimize the environmental impact on forests and greenhouse gases from inefficient combustion of biomass, the Rwanda Ministry of Health (MOH) partnered with DelAgua Health (DelAgua), a private social enterprise, to distribute and promote the use of improved cookstoves and advanced water filters to the poorest quarter of households (Ubudehe 1 and 2) nationally, beginning in Western Province under a program branded Tubeho Neza ("Live Well"). The project is privately financed and earns revenue from carbon credits under the United Nations Clean Development Mechanism. METHODS: During a 3-month period in late 2014, over 470,000 people living in over 101,000 households were provided free water filters and cookstoves. Following the distribution, community health workers visited nearly 98 % of households to perform household level education and training activities. Over 87 % of households were visited again within 6 months with a basic survey conducted. Detailed adoption surveys were conducted among a sample of households, 1000 in the first round, 187 in the second. RESULTS: Approximately a year after distribution, reported water filter use was above 90 % (+/-4 % CI) and water present in filter was observed in over 76 % (+/-6 % CI) of households, while the reported primary stove was nearly 90 % (+/-4.4 % CI) and of households cooking at the time of the visit, over 83 % (+/-5.3 % CI) were on the improved stove. There was no observed association between household size and stove stacking behavior. CONCLUSIONS: This program suggests that free distribution is not a determinant of low adoption. It is plausible that continued engagement in households, enabled by Ministry of Health support and carbon financed revenue, contributed to high adoption rates. Overall, the program was able to demonstrate a privately financed, public health intervention can achieve high levels of initial adoption and usage of household level water filtration and improved cookstoves at a large scale.

Interventions to improve water quality for preventing diarrhoea.

BACKGROUND: Diarrhoea is a major cause of death and disease, especially among young children in low-income countries. In these settings, many infectious agents associated with diarrhoea are spread through water contaminated with faeces.In remote and low-income settings, source-based water quality improvement includes providing protected groundwater (springs, wells, and bore holes), or harvested rainwater as an alternative to surface sources (rivers and lakes). Point-of-use water quality improvement interventions include boiling, chlorination, flocculation, filtration, or solar disinfection, mainly conducted at home. OBJECTIVES: To assess the effectiveness of interventions to improve water quality for preventing diarrhoea. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register (11 November 2014), CENTRAL (the Cochrane Library, 7 November 2014), MEDLINE (1966 to 10 November 2014), EMBASE (1974 to 10 November 2014), and LILACS (1982 to 7 November 2014). We also handsearched relevant conference proceedings, contacted researchers and organizations working in the field, and checked references from identified studies through 11 November 2014. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-RCTs, and controlled before-and-after studies (CBA) comparing interventions aimed at improving the microbiological quality of drinking water with no intervention in children and adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We used meta-analyses to estimate pooled measures of effect, where appropriate, and investigated potential sources of heterogeneity using subgroup analyses. We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: Forty-five cluster-RCTs, two quasi-RCTs, and eight CBA studies, including over 84,000 participants, met the inclusion criteria. Most included studies were conducted in low- or middle-income countries (LMICs) (50 studies) with unimproved water sources (30 studies) and unimproved or unclear sanitation (34 studies). The primary outcome in most studies was self-reported diarrhoea, which is at high risk of bias due to the lack of blinding in over 80% of the included studies. Source-based water quality improvementsThere is currently insufficient evidence to know if source-based improvements such as protected wells, communal tap stands, or chlorination/filtration of community sources consistently reduce diarrhoea (one cluster-RCT, five CBA studies, very low quality evidence). We found no studies evaluating reliable piped-in water supplies delivered to households. Point-of-use water quality interventionsOn average, distributing water disinfection products for use at the household level may reduce diarrhoea by around one quarter (Home chlorination products: RR 0.77, 95% CI 0.65 to 0.91; 14 trials, 30,746 participants, low quality evidence; flocculation and disinfection sachets: RR 0.69, 95% CI 0.58 to 0.82, four trials, 11,788 participants, moderate quality evidence). However, there was substantial heterogeneity in the size of the effect estimates between individual studies.Point-of-use filtration systems probably reduce diarrhoea by around a half (RR 0.48, 95% CI 0.38 to 0.59, 18 trials, 15,582 participants, moderate quality evidence). Important reductions in diarrhoea episodes were shown with ceramic filters, biosand systems and LifeStraw® filters; (Ceramic: RR 0.39, 95% CI 0.28 to 0.53; eight trials, 5763 participants, moderate quality evidence; Biosand: RR 0.47, 95% CI 0.39 to 0.57; four trials, 5504 participants, moderate quality evidence; LifeStraw®: RR 0.69, 95% CI 0.51 to 0.93; three trials, 3259 participants, low quality evidence). Plumbed in filters have only been evaluated in high-income settings (RR 0.81, 95% CI 0.71 to 0.94, three trials, 1056 participants, fixed effects model).In low-income settings, solar water disinfection (SODIS) by distribution of plastic bottles with instructions to leave filled bottles in direct sunlight for at least six hours before drinking probably reduces diarrhoea by around a third (RR 0.62, 95% CI 0.42 to 0.94; four trials, 3460 participants, moderate quality evidence).In subgroup analyses, larger effects were seen in trials with higher adherence, and trials that provided a safe storage container. In most cases, the reduction in diarrhoea shown in the studies was evident in settings with improved and unimproved water sources and sanitation. AUTHORS' CONCLUSIONS: Interventions that address the microbial contamination of water at the point-of-use may be important interim measures to improve drinking water quality until homes can be reached with safe, reliable, piped-in water connections. The average estimates of effect for each individual point-of-use intervention generally show important effects. Comparisons between these estimates do not provide evidence of superiority of one intervention over another, as such comparisons are confounded by the study setting, design, and population.Further studies assessing the effects of household connections and chlorination at the point of delivery will help improve our knowledge base. As evidence suggests effectiveness improves with adherence, studies assessing programmatic approaches to optimising coverage and long-term utilization of these interventions among vulnerable populations could also help strategies to improve health outcomes.

Carbon financing of household water treatment: background, operation and recommendations to improve potential for health gains.

Household water treatment (HWT) provides a means for vulnerable populations to take charge of their own drinking water quality as they patiently wait for the pipe to finally reach them. In many low-income countries, however, promoters have not succeeded in scaling up the intervention among the target population or securing its consistent and sustained use. Carbon financing can provide the funding for reaching targeted populations with effective HWT solutions and the incentives to ensure their long-term uptake. Nevertheless, programs have been criticized because they do not actually reduce carbon emissions. We summarize the background and operation of carbon financing of HWT interventions, including the controversial construct of "suppressed demand". We agree that these programs have limited potential to reduce greenhouse gas emissions and that their characterization of trading "carbon for water" is misleading. Nevertheless, we show that the Kyoto Protocol expressly encouraged the use of suppressed demand as a means of allowing low-income countries to benefit from carbon financing provided it is used to advance development priorities such as health. We conclude by recommending changes to existing criteria for eligible HWT programs that will help ensure that they meet the conditions of microbiological effectiveness and actual use that will improve their potential for health gains.

Human Milk Composition Is Associated with Maternal Body Mass Index in a Cross-Sectional, Untargeted Metabolomics Analysis of Human Milk from Guatemalan Mothers.

Background: Maternal overweight and obesity has been associated with poor lactation performance including delayed lactogenesis and reduced duration. However, the effect on human milk composition is less well understood. Objectives: We evaluated the relationship of maternal BMI on the human milk metabolome among Guatemalan mothers. Methods: We used data from 75 Guatemalan mothers who participated in the Household Air Pollution Intervention Network trial. Maternal BMI was measured between 9 and <20 weeks of gestation. Milk samples were collected at a single time point using aseptic collection from one breast at 6 mo postpartum and analyzed using high-resolution mass spectrometry. A cross-sectional untargeted high-resolution metabolomics analysis was performed by coupling hydrophilic interaction liquid chromatography (HILIC) and reverse phase C18 chromatography with mass spectrometry. Metabolic features associated with maternal BMI were determined by a metabolome-wide association study (MWAS), adjusting for baseline maternal age, education, and dietary diversity, and perturbations in metabolic pathways were identified by pathway enrichment analysis. Results: The mean age of participants at baseline was 23.62 ± 3.81 y, and mean BMI was 24.27 ± 4.22 kg/m2. Of the total metabolic features detected by HILIC column (19,199 features) and by C18 column (11,594 features), BMI was associated with 1026 HILIC and 500 C18 features. Enriched pathways represented amino acid metabolism, galactose metabolism, and xenobiotic metabolic metabolism. However, no significant features were identified after adjusting for multiple comparisons using the Benjamini-Hochberg false discovery rate procedure (FDRBH < 0.2). Conclusions: Findings from this untargeted MWAS indicate that maternal BMI is associated with metabolic perturbations of galactose metabolism, xenobiotic metabolism, and xenobiotic metabolism by cytochrome p450 and biosynthesis of amino acid pathways. Significant metabolic pathway alterations detected in human milk were associated with energy metabolism-related pathways including carbohydrate and amino acid metabolism.This trial was registered at clinicaltrials.gov as NCT02944682.

Cooking with liquefied petroleum gas or biomass and fetal growth outcomes: a multi-country randomised controlled trial.

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. We conducted ultrasound assessments at baseline, 24-28 weeks of gestation (the first pregnancy visit), and 32-36 weeks of gestation (the second pregnancy visit), to measure fetal size; we monitored 24 h personal exposures to household air pollutants during these visits; and we weighed children at birth. We conducted intention-to-treat analyses to estimate differences in fetal size between the intervention and control group, and exposure-response analyses to identify associations between household air pollutants and fetal size. This trial is registered with ClinicalTrials.gov (NCT02944682). FINDINGS: Between May 7, 2018, and Feb 29, 2020, we randomly assigned 3200 pregnant women (1593 to the intervention group and 1607 to the control group). The mean gestational age was 14·5 (SD 3·0) weeks and mean maternal age was 25·6 (4·5) years. We obtained ultrasound assessments in 3147 (98·3%) women at baseline, 3052 (95·4%) women at the first pregnancy visit, and 2962 (92·6%) at the second pregnancy visit, through to Aug 25, 2020. Intervention adherence was high (the median proportion of days with biomass stove use was 0·0%, IQR 0·0-1·6) and pregnant women in the intervention group had lower mean exposures to particulate matter with a diameter less than 2·5 µm (PM2·5; 35·0 [SD 37·2] µg/m3vs 103·3 [97·9] µg/m3) than did women in the control group. We did not find differences in averaged post-randomisation Z scores for head circumference (0·30 vs 0·39; p=0·04), abdominal circumference (0·38 vs 0·39; p=0·99), femur length (0·44 vs 0·45; p=0·73), and estimated fetal weight or birthweight (-0·13 vs -0·12; p=0·70) between the intervention and control groups. Personal exposures to household air pollutants were not associated with fetal size. INTERPRETATION: Although an LPG cooking intervention successfully reduced personal exposure to air pollution during pregnancy, it did not affect fetal size. Our findings do not support the use of unvented liquefied petroleum gas stoves as a strategy to increase fetal growth in settings were biomass fuels are used predominantly for cooking. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Kinyarwanda, Spanish and Tamil translations of the abstract see Supplementary Materials section.

Effects of a liquefied petroleum gas stove intervention on stillbirth, congenital anomalies and neonatal mortality: A multi-country household air pollution intervention network trial.

Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM2.5), black carbon (BC) and carbon monoxide (CO) and these outcomes. Pregnant women (18 to <35 years of age; gestation confirmed by ultrasound at 9 to <20 weeks) were randomly assigned to intervention or control arms. We monitored these fetal and neonatal outcomes and personal exposure to PM2.5, BC and CO three times during pregnancy, we conducted intention-to-treat (ITT) and exposure-response (E-R) analyses to determine if the HAPIN intervention and corresponding HAP exposure was associated with the risk of fetal/neonatal outcomes. A total of 3200 women (mean age 25.4 ± 4.4 years, mean gestational age at randomization 15.4 ± 3.1 weeks) were included in this analysis. Relative risks for stillbirth, congenital anomaly and neonatal mortality were 0.99 (0.60, 1.66), 0.92 (95 % CI 0.52, 1.61), and 0.99 (0.54, 1.85), respectively, among women in the intervention arm compared to controls in an ITT analysis. Higher mean personal exposures to PM2.5, CO and BC during pregnancy were associated with a higher, but statistically non-significant, incidence of adverse outcomes. The LPG stove and fuel intervention did not reduce the risk of these outcomes nor did we find evidence supporting an association between personal exposures to HAP and stillbirth, congenital anomalies and neonatal mortality.

Study design and rationale for the PAASIM project: a matched cohort study on urban water supply improvements and infant enteric pathogen infection, gut microbiome development and health in Mozambique.

INTRODUCTION: Despite clear linkages between provision of clean water and improvements in child health, limited information exists about the health impacts of large water infrastructure improvements in low-income settings. Billions of dollars are spent annually to improve urban water supply, and rigorous evaluation of these improvements, especially targeting informal settlements, is critical to guide policy and investment strategies. Objective measures of infection and exposure to pathogens, and measures of gut function, are needed to understand the effectiveness and impact of water supply improvements. METHODS AND ANALYSIS: In the PAASIM study, we examine the impact of water system improvements on acute and chronic health outcomes in children in a low-income urban area of Beira, Mozambique, comprising 62 sub-neighbourhoods and ~26 300 households. This prospective matched cohort study follows 548 mother-child dyads from late pregnancy through 12 months of age. Primary outcomes include measures of enteric pathogen infections, gut microbiome composition and source drinking water microbiological quality, measured at the child's 12-month visit. Additional outcomes include diarrhoea prevalence, child growth, previous enteric pathogen exposure, child mortality and various measures of water access and quality. Our analyses will compare (1) subjects living in sub-neighbourhoods with the improved water to those living in sub-neighbourhoods without these improvements; and (2) subjects with household water connections on their premises to those without such a connection. This study will provide critical information to understand how to optimise investments for improving child health, filling the information gap about the impact of piped water provision to low-income urban households, using novel gastrointestinal disease outcomes. ETHICS AND DISSEMINATION: This study was approved by the Emory University Institutional Review Board and the National Bio-Ethics Committee for Health in Mozambique. The pre-analysis plan is published on the Open Science Framework platform (https://osf.io/4rkn6/). Results will be shared with relevant stakeholders locally, and through publications.

Lung Ultrasound Protocol and Quality Control of Image Interpretation Using an Adjudication Panel in the Household Air Pollution Intervention Network (HAPIN) Trial.

OBJECTIVE: Lung ultrasound (LUS) is an alternative to chest radiography to confirm a diagnosis of pneumonia. For research and disease surveillance, methods to use LUS to diagnose pneumonia are needed. METHODS: In the Household Air Pollution Intervention Network (HAPIN) trial, LUS was used to confirm a clinical diagnosis of severe pneumonia in infants. We developed a standardized definition of pneumonia, protocols for recruitment and training of sonographers, along with LUS image acquisition and interpretation. We use a blinded panel approach to interpretation with LUS cine-loops randomized to non-scanning sonographers with expert review. DISCUSSION: We obtained 357 lung ultrasound scans: 159, 8 and 190 scans were collected in Guatemala, Peru and Rwanda, respectively. The diagnosis of primary endpoint pneumonia (PEP) required an expert tie breaker in 181 scans (39%). PEP was diagnosed in 141 scans (40%), not diagnosed in 213 (60%), with 3 scans (<1%) deemed uninterpretable. Agreement among the two blinded sonographers and the expert reader in Guatemala, Peru and Rwanda was 65%, 62% and 67%, with a prevalence-and-bias-corrected kappa of 0.30, 0.24 and 0.33, respectively. CONCLUSION: Use of standardized imaging protocols, training and an adjudication panel resulted in high confidence for the diagnosis of pneumonia using LUS.